scholarly journals Collective cancer cell invasion requires RNA accumulation at the invasive front

2020 ◽  
Vol 117 (44) ◽  
pp. 27423-27434 ◽  
Author(s):  
George Chrisafis ◽  
Tianhong Wang ◽  
Konstadinos Moissoglu ◽  
Alexander N. Gasparski ◽  
Yeap Ng ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Single Cells ◽  
Three Dimensional ◽  
Nucleotide Exchange ◽  
Cancer Cell Invasion ◽  
Invasive Front ◽  
Rna Accumulation

Localization of RNAs at protrusive regions of cells is important for single-cell migration on two-dimensional surfaces. Protrusion-enriched RNAs encode factors linked to cancer progression, such as the RAB13 GTPase and the NET1 guanine nucleotide exchange factor, and are regulated by the tumor-suppressor protein APC. However, tumor cells in vivo often do not move as single cells but rather utilize collective modes of invasion and dissemination. Here, we developed an inducible system of three-dimensional (3D) collective invasion to study the behavior and importance of protrusion-enriched RNAs. We find that, strikingly, both theRAB13andNET1RNAs are enriched specifically at the invasive front of leader cells in invasive cell strands. This localization requires microtubules and coincides with sites of high laminin concentration. Indeed, laminin association and integrin engagement are required for RNA accumulation at the invasive front. Importantly, perturbing RNA accumulation reduces collective 3D invasion. Examination of in vivo tumors reveals a similar localization of theRAB13andNET1RNAs at potential invasive sites, suggesting that this mechanism could provide a targeting opportunity for interfering with collective cancer cell invasion.

scholarly journals Quantitative real-time imaging of molecular dynamics during cancer cell invasion and metastasis in vivo

2009 ◽  
Vol 3 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Paul Timpson ◽  
Alan Serrels ◽  
Marta Canel ◽  
Margaret C. Frame ◽  
Valerie G. Brunton ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Real Time ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Real Time Imaging

scholarly journals TP53 drives invasion through expression of its Δ133p53β variant

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Gilles Gadea ◽  
Nikola Arsic ◽  
Kenneth Fernandes ◽  
Alexandra Diot ◽  
Sébastien M Joruiz ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Tp53 Mutation ◽  
P53 Protein ◽  
Clinical Analysis ◽  
Breast Cancer Patients ◽  
Cancer Cell Invasion ◽  
Mutation Status ◽  
Risk Of Cancer

TP53 is conventionally thought to prevent cancer formation and progression to metastasis, while mutant TP53 has transforming activities. However, in the clinic, TP53 mutation status does not accurately predict cancer progression. Here we report, based on clinical analysis corroborated with experimental data, that the p53 isoform Δ133p53β promotes cancer cell invasion, regardless of TP53 mutation status. Δ133p53β increases risk of cancer recurrence and death in breast cancer patients. Furthermore Δ133p53β is critical to define invasiveness in a panel of breast and colon cell lines, expressing WT or mutant TP53. Endogenous mutant Δ133p53β depletion prevents invasiveness without affecting mutant full-length p53 protein expression. Mechanistically WT and mutant Δ133p53β induces EMT. Our findings provide explanations to 2 long-lasting and important clinical conundrums: how WT TP53 can promote cancer cell invasion and reciprocally why mutant TP53 gene does not systematically induce cancer progression.

Micropassage-embedding composite hydrogel fibers enable quantitative evaluation of cancer cell invasion under 3D coculture conditions

Lab on a Chip ◽  
2018 ◽  
Vol 18 (9) ◽  
pp. 1378-1387 ◽  
Author(s):  
Manami Sugimoto ◽  
Yoichi Kitagawa ◽  
Masumi Yamada ◽  
Yuya Yajima ◽  
Rie Utoh ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Quantitative Evaluation ◽  
Cell Invasion ◽  
Three Dimensional ◽  
Composite Hydrogel ◽  
Cancer Cell Invasion ◽  
New System

A new system for quantitatively evaluating cancer cell invasion in a three-dimensional environment was developed using composite hydrogel microfibers having a micropassage.

scholarly journals Dynamics of 3D carcinoma cell invasion into aligned collagen

2018 ◽  
Vol 10 (2) ◽  
pp. 100-112 ◽  
Author(s):  
Arja Ray ◽  
Rachel K. Morford ◽  
Nima Ghaderi ◽  
David J. Odde ◽  
Paolo. P. Provenzano
Keyword(s):  
Extracellular Matrix ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Carcinoma Cell ◽  
Spatiotemporal Dynamics ◽  
Contact Inhibition ◽  
Contact Guidance ◽  
Cell Behavior ◽  
Cancer Cell Invasion ◽  
Invasive Front

We present a novel platform to quantify spatiotemporal dynamics of cell behavior at and beyond the invasive front and demonstrate that contact inhibition and contact guidance orchestrate cancer cell invasion into anisotropic extracellular matrix.

scholarly journals 3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo

2003 ◽  
Vol 88 (7) ◽  
pp. 1111-1118 ◽  
Author(s):  
I Kempen ◽  
D Papapostolou ◽  
N Thierry ◽  
L Pochet ◽  
S Counerotte ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Tumour Growth ◽  
Cancer Cell Invasion

scholarly journals BSCI-10. Invasive growth of brain metastases is driven by cancer cell-pSTAT3+ reactive astrocyte crosstalk

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii3-iii3
Author(s):  
Matthew Dankner ◽  
Sarah Maritan ◽  
Rebecca Zhuang ◽  
Maxime Caron ◽  
Neibla Priego ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Brain Slice ◽  
Invasive Growth ◽  
Cancer Cell Invasion ◽  
Genetic Ablation ◽  
Brain Slice Cultures ◽  
Stat3 Inhibition

Abstract Background Brain metastases (BrM) with a highly invasive (HI) histological growth pattern are associated with poor prognosis compared to minimally invasive (MI) masses. Compared to MI lesions, HI BrM form greater contacts with cells in the peritumoral brain, particularly reactive astrocytes (RAs). RAs expressing phosphorylated STAT3 (pSTAT3+RAs) have been shown to promote BrM colonization. Here, we investigate the role of pSTAT3+RAs in promoting invasive growth of HI BrM. Methods We performed immunohistochemistry to identify pSTAT3+RAs in HI and MI human and patient-derived xenograft BrM. We assessed how pharmacological STAT3 inhibition or RA-specific STAT3 genetic ablation affected HI and MI BrM growth in vivo. scRNA-seq data generated from HI BrM astrocytes were integrated with published RA secretome data to identify STAT3 targets expressed by RAs that may drive invasion. Cancer cell invasion was modeled in vitro using a brain slice-tumor co-culture assay. Results HI BrM display increased pSTAT3-positivity within RAs when compared to MI lesions. Pharmacological STAT3 inhibition with Legasil (Silibinin) or genetic ablation decreased in vivo growth of HI, but not MI, BrM. Brain slice cultures treated with STAT3-activating cytokines induced cancer cell invasion, a response that was ablated following STAT3 inhibition. Chi3L1 was identified as a STAT3 target expressed by RAs. Cancer cells treated with recombinant Chi3L1 showed greater invasion into brain slice cultures compared to untreated cells. Conclusions pSTAT3+RAs are over-represented in HI BrM, rendering HI BrM preferentially sensitive to STAT3 inhibition. pSTAT3+RAs functionally contribute to BrM invasion within the brain, in part through Chi3L1-mediated activity. This work identifies STAT3 and Chi3L1 as clinically relevant therapeutic targets in management of HI BrM.

scholarly journals Cancer Invasion: Patterns and Mechanisms

Acta Naturae ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 17-28 ◽  
Author(s):  
N. V. Krakhmal ◽  
M. V. Zavyalova ◽  
E. V. Denisov ◽  
S. V. Vtorushin ◽  
V. M. Perelmuter
Keyword(s):  
Cell Migration ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cell Invasion ◽  
Cancer Invasion ◽  
Collective Cell Migration ◽  
Cancer Cell Migration ◽  
Cancer Cell Invasion ◽  
Invasion Patterns

Cancer invasion and the ability of malignant tumor cells for directed migration and metastasis have remained a focus of research for many years. Numerous studies have confirmed the existence of two main patterns of cancer cell invasion: collective cell migration and individual cell migration, by which tumor cells overcome barriers of the extracellular matrix and spread into surrounding tissues. Each pattern of cell migration displays specific morphological features and the biochemical/molecular genetic mechanisms underlying cell migration. Two types of migrating tumor cells, mesenchymal (fibroblast-like) and amoeboid, are observed in each pattern of cancer cell invasion. This review describes the key differences between the variants of cancer cell migration, the role of epithelial-mesenchymal, collective-amoeboid, mesenchymal-amoeboid, and amoeboid-mesenchymal transitions, as well as the significance of different tumor factors and stromal molecules in tumor invasion. The data and facts collected are essential to the understanding of how the patterns of cancer cell invasion are related to cancer progression and therapy efficacy. Convincing evidence is provided that morphological manifestations of the invasion patterns are characterized by a variety of tissue (tumor) structures. The results of our own studies are presented to show the association of breast cancer progression with intratumoral morphological heterogeneity, which most likely reflects the types of cancer cell migration and results from different activities of cell adhesion molecules in tumor cells of distinct morphological structures.

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